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Research Article | Volume 11 Issue 5 (May, 2025) | Pages 886 - 891
Clinicopathological Correlation of Cutaneous Manifestations in Patients with Systemic Autoimmune Disorders: An Observational Study in a Tertiary Care Center
 ,
 ,
1
Associate Professor, Department of Pathology, Government Medical College, Kamareddy, Telangana, India
2
Associate Professor, Department of DVL, Government Medical College, Kamareddy, Telangana, India
3
Associate Professor, Department of General Medicine, Government Medical College, Kamareddy, Telangana, India
Under a Creative Commons license
Open Access
Received
March 28, 2025
Revised
April 23, 2025
Accepted
April 27, 2025
Published
May 13, 2025
Abstract

Background: Cutaneous manifestations are often the first indicator of underlying systemic autoimmune disorders. Recognizing and correlating these with histopathological and immunological findings can facilitate early diagnosis and management. Objectives: To evaluate the spectrum of cutaneous manifestations in patients with systemic autoimmune disorders and correlate clinical features with histopathological and serological profiles. Methods: This cross-sectional observational study included 100 patients with confirmed systemic autoimmune diseases and cutaneous involvement attending the dermatology and rheumatology clinics at a tertiary care center. Detailed clinical evaluation, laboratory investigations, autoantibody profiling, and skin biopsies (where indicated) were performed. The data were tabulated and statistically analyzed. Results: Of the 100 patients, 78% were female with a mean age of 39.4 ± 12.7 years. The most common systemic autoimmune condition was systemic lupus erythematosus (44%), followed by systemic sclerosis (20%) and dermatomyositis (12%). Photosensitivity (35%) and malar rash (32%) were the most frequent cutaneous findings. Histopathological analysis (n=60) revealed interface dermatitis (43.3%) and basal cell vacuolization (30%) as predominant features. ANA positivity was seen in 90% of patients, with disease-specific autoantibodies (anti-dsDNA, anti-Ro/SSA, anti-Scl-70) correlating with respective clinical patterns. Conclusion: Cutaneous features in systemic autoimmune disorders show distinct clinical and pathological patterns. Timely recognition and biopsy evaluation of skin lesions, along with autoantibody profiling, play a vital role in early diagnosis and management.

Keywords
INTRODUCTION

Systemic autoimmune disorders are chronic, multisystem diseases characterized by aberrant immune responses targeting self-antigens, often leading to inflammation and damage across various organs. Among the earliest and most visible signs of these conditions are cutaneous manifestations, which frequently serve as important clinical clues for diagnosis and disease monitoring. The skin, being an immunologically active organ, often reflects the underlying immunopathology of systemic diseases such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), dermatomyositis, and others.

 

Cutaneous features in autoimmune diseases are highly variable, ranging from non-specific findings like xerosis to disease-defining lesions such as malar rash, Gottron’s papules, and sclerodactyly. These manifestations are not only diagnostic markers but may also correlate with internal organ involvement and disease severity. Histopathological evaluation of skin lesions can offer valuable insights into the nature and extent of dermal and epidermal involvement, while immunological assays help in identifying disease-specific autoantibodies that strengthen clinical diagnoses.

 

Despite the clinical significance of skin involvement in systemic autoimmune diseases, the correlation between cutaneous findings, histopathology, and autoantibody profiles remains underexplored in many regional populations. A comprehensive clinicopathological approach is essential to enhance early diagnosis, appropriate classification, and timely therapeutic intervention.

 

This study was undertaken to analyze the spectrum of cutaneous manifestations in patients with systemic autoimmune disorders and to establish a clinicopathological and serological correlation, thereby contributing to improved diagnostic and prognostic understanding in a tertiary care setting.

METHODOLOGY

Study Design and Setting:

This was a hospital-based cross-sectional observational study conducted in the Departments of Dermatology and General Medicine at Government Medical College, Kamareddy, a tertiary care teaching hospital in Telangana, India.

 

Study Duration:

The study was carried out over a period of nine months, from May 2024 to January 2025.

 

Study Population:

A total of 100 patients presenting with cutaneous manifestations associated with systemic autoimmune disorders were enrolled consecutively during the study period. All patients were either outpatients or inpatients evaluated in the Dermatology or Rheumatology clinics.

 

Inclusion Criteria:

  • Patients aged 18 years and above.
  • Clinically diagnosed or serologically confirmed cases of systemic autoimmune diseases (e.g., SLE, systemic sclerosis, dermatomyositis, mixed connective tissue disease, Sjögren’s syndrome, rheumatoid arthritis).
  • Presence of cutaneous lesions related to the underlying autoimmune condition.
  • Willingness to provide written informed consent.

 

Exclusion Criteria:

  • Patients with only localized autoimmune skin disorders (e.g., localized scleroderma, discoid lupus without systemic features).
  • Patients with cutaneous manifestations due to infections, malignancy, or drug reactions.
  • Incomplete clinical or laboratory data.

 

Data Collection:

A detailed clinical history and dermatological examination were performed for each patient, and relevant systemic examination findings were documented. Cutaneous lesions were classified based on morphology and distribution.

 

Investigations:

Routine blood investigations, including complete blood count, ESR, renal and liver function tests.

 

Autoantibody profile including ANA, anti-dsDNA, anti-Ro/SSA, anti-Sm, anti-Scl-70, and rheumatoid factor using ELISA or immunofluorescence.

 

Skin biopsies were performed in 60 patients after obtaining informed consent. Histopathological examination was done by an experienced pathologist using hematoxylin and eosin staining.

 

Ethical Considerations:

Institutional Ethics Committee (IEC) approval was obtained prior to the commencement of the study. All patients provided written informed consent.

 

Statistical Analysis:

Data were entered in Microsoft Excel and analyzed using SPSS software. Descriptive statistics (frequency, percentage, mean ± SD) were used. Clinicopathological and serological correlations were assessed and presented in tabular form.

RESULTS

A total of 100 patients with systemic autoimmune disorders presenting with cutaneous manifestations were enrolled in the study. The majority of participants were female (78%), with a female-to-male ratio of approximately 3.5:1. The mean age of the study population was 39.4 ± 12.7 years. A slight urban predominance was observed (56%) compared to rural (44%) (Table 1).

 

Table 1: Demographic Profile of Study Participants (n=100)

Variable

Frequency

Gender - Female

78

Gender - Male

22

Urban Residence

56

Rural Residence

44

Mean Age (years)

39.4 ± 12.7

 

The most common systemic autoimmune disorder identified was Systemic Lupus Erythematosus (SLE), accounting for 44% of cases, followed by Systemic Sclerosis (20%), Dermatomyositis (12%), and Mixed Connective Tissue Disease (10%). Less common conditions included Sjögren’s Syndrome (8%) and Rheumatoid Arthritis with cutaneous manifestations (6%) (Table 2).

 

Table 2: Spectrum of Systemic Autoimmune Disorders

Autoimmune Disorder

Frequency

Percentage (%)

Systemic Lupus Erythematosus (SLE)

44

44%

Systemic Sclerosis (SSc)

20

20%

Dermatomyositis

12

12%

Mixed Connective Tissue Disease (MCTD)

10

10%

Sjögren’s Syndrome

8

8%

Rheumatoid Arthritis with Cutaneous Manifestations

6

6%

 

Cutaneous involvement was diverse, with photosensitivity (35%) being the most frequently reported manifestation, followed by malar rash (32%), Raynaud’s phenomenon (28%), and skin tightening or sclerodactyly (20%). Other notable findings included discoid rash (18%), nailfold capillary changes (16%), vasculitic ulcers (14%), xerosis (11%), and hallmark signs of dermatomyositis such as Gottron’s papules (10%) and heliotrope rash (9%) (Table 3).

 

Table 3: Cutaneous Manifestations Observed

Cutaneous Feature

Frequency

Percentage (%)

Photosensitivity

35

35%

Malar rash

32

32%

Raynaud’s phenomenon

28

28%

Discoid rash

18

18%

Skin tightening/sclerodactyly

20

20%

Nailfold capillary changes

16

16%

Vasculitic ulcers or purpura

14

14%

Xerosis or ichthyosis

11

11%

Gottron’s papules

10

10%

Heliotrope rash

9

9%

Livedo reticularis

8

8%

 

Histopathological examination was conducted in 60 patients, revealing that the most prevalent feature was interface dermatitis (43.3%), particularly in patients with SLE and dermatomyositis. Other findings included basal cell vacuolization (30%), fibrinoid necrosis of vessels (23.3%), dermal fibrosis (20%), and mucin deposition (16.7%), suggesting distinct patterns associated with the underlying autoimmune pathology (Table 4).

 

Table 4: Histopathological Findings (n=60 biopsied cases)

Histopathological Finding

Number of Cases

Percentage (%)

Interface dermatitis

26

43.3%

Basal cell vacuolization

18

30%

Fibrinoid necrosis of vessels (vasculitis)

14

23.3%

Dermal fibrosis

12

20%

Mucin deposition

10

16.7%

 

Autoantibody profiling demonstrated a high positivity rate for antinuclear antibodies (ANA) (90%), consistent with the autoimmune nature of the cohort. Specific autoantibodies such as anti-dsDNA (38%), anti-Ro/SSA (22%), anti-Scl-70 (18%), anti-Sm (15%), and rheumatoid factor (10%) were detected in varying proportions, correlating well with respective disease types (Table 5).

 

Table 5: Autoantibody Profile

Autoantibody

Positive Cases (n=100)

Percentage (%)

ANA

90

90%

Anti-dsDNA

38

38%

Anti-Ro/SSA

22

22%

Anti-Scl-70

18

18%

Anti-Sm

15

15%

Rheumatoid Factor

10

10%

DISCUSSION

This observational study conducted at Government Medical College, Kamareddy, provides valuable insights into the cutaneous manifestations of systemic autoimmune disorders and their clinicopathological and immunological correlations. Among the 100 patients evaluated, females constituted 78% of the cohort, reaffirming the well-documented female predominance in autoimmune conditions such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and Sjögren’s syndrome. The mean age of presentation (39.4 ± 12.7 years) aligns with global trends where autoimmune diseases typically manifest during the third to fifth decades of life [7].

 

SLE was the most frequently encountered autoimmune disorder in this study (44%), followed by SSc (20%) and dermatomyositis (12%). These findings are consistent with previous multicenter studies, including those from Indian and international cohorts, which highlight SLE as a major contributor to autoimmune-related skin disease [8,9]. The most prevalent cutaneous features observed were photosensitivity (35%), malar rash (32%), and Raynaud’s phenomenon (28%), all of which are well-established dermatologic markers in SLE and other connective tissue diseases [10].

 

Histopathological evaluation revealed interface dermatitis and basal cell vacuolization as the most common patterns, particularly in patients with SLE and dermatomyositis. In contrast, dermal fibrosis and mucin deposition were frequently noted in patients with systemic sclerosis. These observations correlate with previous histopathological studies that emphasize the diagnostic utility of skin biopsies in detecting early systemic involvement [11].

 

Autoantibody profiling demonstrated a high ANA positivity (90%), further validating its role as a sensitive but nonspecific marker. Specific autoantibodies such as anti-dsDNA (38%), anti-Scl-70 (18%), and anti-Ro/SSA (22%) showed strong disease associations, enhancing diagnostic confidence. These serological findings are in agreement with earlier studies that emphasize the value of immunological markers in differentiating subtypes of autoimmune diseases and predicting organ involvement [10].

 

This study reinforces the concept that cutaneous manifestations may precede or occur concurrently with systemic involvement, thereby offering a critical diagnostic window into autoimmune pathology. The integration of clinical dermatologic assessment, histopathology, and serological profiling not only enhances early recognition but also facilitates comprehensive and timely patient management. Multidisciplinary collaboration among dermatologists, pathologists, and rheumatologists is essential for optimal care in patients presenting with autoimmune cutaneous disease

 

Limitations:
This study was limited by its single-center design and modest sample size. Histopathological analysis was performed in only 60 patients, which may underrepresent some findings. Longitudinal follow-up to assess therapeutic response and disease progression was not included.

CONCLUSION

This study highlights the clinical significance of cutaneous manifestations as early and reliable indicators of systemic autoimmune diseases. A high prevalence of photosensitivity, malar rash, and Raynaud’s phenomenon was observed, particularly among patients with SLE and systemic sclerosis. Histopathological findings such as interface dermatitis and basal cell vacuolization, along with serological markers like ANA and anti-dsDNA, demonstrated strong diagnostic correlations. Skin lesions, when evaluated comprehensively, can aid in early diagnosis and disease classification. Integrating dermatological, pathological, and immunological assessments enhances clinical precision and patient care. Multidisciplinary collaboration and awareness are essential for the timely recognition and management of systemic autoimmune disorders presenting with cutaneous features.

REFERENCES
  1. Masi AT, Kaslow RA. Sex effects in SLE: A clue to pathogenesis. Arthritis Rheum. 1978;21:480.
  2. Malaviya AN, Singh RR, Kumar De A, Kumar A, Aradhye S. SLE in Northern India: A review of 329 cases. J Assoc Physicians India. 1988;36:476–80.
  3. Wysenbeek AJ, Guedj D, Amit M, Weinberger A. Rash in SLE: Prevalence and cutaneous and noncutaneous manifestations. Ann Rheum Dis. 1992;51:717–9.
  4. Tebbe B, Mansmann U, Wollina U, Auer-Grumbach P, Licht-Mbalyohere A, Arensmeier M, et al. Markers in cutaneous lupus erythematosus indicating systemic involvement: A multicenter study on 296 patients. Acta Derm Venereol. 1997;77:305–8.
  5. Parodi A, Rebora A. ARA and EADV criteria for classification of systemic lupus erythematosus in patients with cutaneous lupus erythematosus. Dermatology. 1997;194:217–20.
  6. Sirka CS, Padhi T, Mohanty P, Patel DK, Parida PR, Kar CR. Bullous systemic lupus erythematosus: Response to dapsone in two patients. Indian J Dermatol Venereol Leprol. 2005;71:54–6.
  7. Cervera R, Khamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P, et al. Morbidity and mortality in systemic lupus erythematosus during a 10-year period: A comparison of early and late manifestations in a cohort of 1,000 patients. Medicine (Baltimore). 2003;82:299–308.
  8. Wallace DJ, Pistiner M, Nessim S, Metzger AL, Klinenberg JR. Cutaneous lupus erythematosus without systemic lupus erythematosus: Clinical and laboratory features. Semin Arthritis Rheum. 1992;21:221–6.
  9. Akrekar SM, Bichile LS. Cutaneous vasculitis in lupus: A turning point in the history of the disease? A case report and review of literature. J Indian Rheumatol Assoc. 2005;13:29–31.
  10. Ghosh AP, Nag F, Biswas S, Rao R, De A. Clinicopathological and Immunological Profile of Patients with Cutaneous Manifestations and their Relationship with Organ Involvement in Systemic Lupus Erythematosus Attending a Tertiary Care Center of Eastern India. Indian J Dermatol. 2020 Jan-Feb;65(1):22-28. doi: 10.4103/ijd.IJD_282_19. PMID: 32029935; PMCID: PMC6986128.
  11. Frumholtz L, Laurent-Roussel S, Aumaître O, Maurier F, Le Guenno G, Carlotti A, Dallot A, Kemeny JL, Antunes L, Froment N, Fraitag S, London J, Berezne A, Terris B, Le Jeunne C, Mouthon L, Aractingi S, Guillevin L, Dupin N, Terrier B; French Vasculitis Study Group. Clinical and pathological significance of cutaneous manifestations in ANCA-associated vasculitides. Autoimmun Rev. 2017 Nov;16(11):1138-1146. doi: 10.1016/j.autrev.2017.09.009. Epub 2017 Sep 14. PMID: 28918161.
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